The protective effect of sesamol against mitochondrial oxidative stress and hepatic injury in acetaminophen-overdosed rats.
An acetaminophen (APAP) overdose induces oxidative stress and acute hepatic injury or even death. We investigated the prophylactic effect of sesamol (SM) on mitochondrial oxidative stress, hydroxyl-radical-generated lipid peroxidation, and hepatic injury in APAP-overdosed rats. Six male Wistar rats (APAP group) were given only oral APAP (1,000 mg/kg) to induce mitochondrial oxidative-stress-associated hepatic injury, and another six (ASM group) were given the same dose of oral APAP, and then, immediately afterward, were injected with SM (10 mg/kg, i.p.), to assess its prophylactic effects. In the APAP group, APAP had significantly increased the levels of 1) serum aspartate transaminase and alanine transaminase, 2) centrilobular necrosis, 3) ferrous ions, 4) hydrogen peroxide, 5) hydroxyl radicals, and 6) lipid peroxidation, and decreased 7) mitochondrial aconitase activity in the rats' liver tissue 24 h later. In the ASM group, SM had prevented significant rises in the levels of 1) to 6) and a significant decrease (7). Therefore, we hypothesize that the protective effect of SM in APAP-overdosed rats is associated with maintaining the mitochondrial aconitase activity, ferrous ions (Fe2+), and hydrogen peroxide levels and inhibiting hydroxyl-radical-associated lipid peroxidation and hepatic injury.
Chandrasekaran
Victor Raj Mohan
VR
Department of Environmental and Occupational Health, National Cheng Kung University, Tainan, Taiwan.
Hsu
Dur-Zong
DZ
Liu
Ming-Yie
MY
D000082:Acetaminophen / Q000633:toxicity*; D018712:Analgesics, Non-Narcotic / Q000633:toxicity*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D052117:Benzodioxoles / Q000494:pharmacology*; D006861:Hydrogen Peroxide / Q000378:metabolism; D017665:Hydroxyl Radical / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects*; D010636:Phenols / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D018712:Analgesics, Non-Narcotic; D000975:Antioxidants; D052117:Benzodioxoles; D010636:Phenols; D017665:Hydroxyl Radical; D000082:Acetaminophen; C025583:sesamol; D006861:Hydrogen Peroxide